Carbalkoxylation of organic compounds



UNITED STATES PATENT OFFICE CARBALKOXYLATION OF ORGANIC COMPOUNDS Vernon H. Wallingford, Ferguson, and August H. Homeyer, Webster Groves, Mo., assignors to Mallinckrodt Chemical Works, St. Louis, Mo., a corporation of Missouri No Drawing. Original application July 30 1942,

Serial No. 452,916. Divided and this application January 10, 1945, Serial No. 572,262

1 7 Claims. (01. 260-475) 2 This invention relates to the carbalkoxylation group, R' is an organic esterifying radical, R' of organic compounds, and with respect to ceris the alkyl of the dialkyl carbonate, M is an tain more specific features to the introduction of alkali metal and R." is the radical of the alcocarbalkoxy groups into certain types of esters. holate. Where R and R' are organic radicals This application is a division of our copending 5 they are preferably non-acidic in character. application Serial No. 452,916, filed July 30, 1942, While the reaction is preferably carried out now Patent No. 2,367,632, anda continuation-inwith a symmetrical dialkyl carbonate as shown part of our applications Serial No. 287,001, filed in the equation, it can be carried out with an July 28, 1939, now Patent No. 2,346,059; Serial unsymmetrical dialkyl carbonate. In such cases, No. 374,254, filed January 13, 1941, now Patent a mixture of carbalkoxylated compounds and No. 2,376,837; Serial No. 375,614, filed January product alcohols may be formed.

23, 1941, now Patent No. 2,342,385 and, Serial The mechanism of the reaction involved in the No. 379,828, filed February 20, 1941, now Patent process of the present invention has not yet been No. 2,407,942. definitely established. The large excess of diakyl Among the several objects of the invention carbonate which is preferred, appears, however, may be noted the provision of a general process to be an important factor. for bringing about a carbalkoxylation of the type The reaction may be pushed to substantial indicated, which is characterized by high yields, completion by heating as it progresses, to distill its inexpensive and readily procurable reaction off the product alcohols (R'OH and R."OH in materials, and the facility with which it may be the above equation). In case the original metal carried out. Other objects will be in part obalcoholate contains alcohol, such alcohol is likevious and in part pointed out hereinafter. wise removed by this distillation procedure. This The invention accordingly comprises the steps procedure, while optional, is highly advantageous and sequence of steps, and features of synthesis, in its improvement in the yield of carbalkanalysis, or metathesis, which will be exemplified oxylated compound obtained.

in the processes hereinafter described, and the When the intended use of the sodio or other scope of the application of which will be indialkali metal compound is the preparation therecated in the following claims. from of an alkyl substituted compound, the sodio While the process of the present invention compound need notbe recovered from the resiprovides primarily for the introduction of a due as such, but the residue may be alkylated cgrbalkoxy group; irito compounds sf the type {so form thedalfkylatettzl1 compound wihitch mag than a ove indica ed, i a so, n many ns ances, pro- 1 e recovere rom e reac ion in x ure. n e duces the carbalkoxylated product in the form other hand, if carbalkoxylation alone is desired, of a highly reactive metallo derivative which the sodio group, for example, may be replaced readily lends itself to'further steps of synthesis. by hydrogen by any suitable method, for ex- Tilllisl itneltalllo tcompollilnld may be then directly an irplabg acidification. 1 m t t t 1 a y a e y he we nown procedures, or if e o ow ng examp es us ra e cer an carbalkoxylation alone is desired, the metallo specific embodiments of the present invention, group may be replaced by hydrogen in the usual 40 but are intended to be by way of example only: way. The metal of such a group is usually and preferably one of the alkali metals. EXAMPLE 1 Broadly speaking the process of the present Ethyl phenylacetate invention comprises the carbalkoxylation of i h 1 b t (450 1) I d I esters of the type subsequently described D et y car ona e m. was p ace :1 a through the reaction of such an ester, 9, dialkyl 1 liter, three-necked flask fitted with a mechanicarbonate and a metal alcoholate, in the dialkyl 08.1 stirrer. Solid alcohol-free sodium methylate carbonate, preferably in substantial excess, as (43 8- a d ethyl p y te (123 8-) were the reaction medium. This may be represented dd d- The i tu became y l w a d th r by the following equation: was a little heat of reaction. By warming gently, all1 21f theTslod;1umkmeth3;ltatehvgats brguglt into so u on. e as was a ac e o a rac iona ing column arranged for distillation at mm.

where R is selected from hydrogen and organic pressure. Alcohol was obtained as distillate at radicals which do not possess an aliphatic multi- 6 first, and then the temperature rose to 72 C. at ply bonded carbon atom adjacent to the CH: 175 mm. at the head of the column, which correwater layer was separated and extracted with a little ether. The organic layers were combined, washed with water, dried over calcium chloride and distilled, yielding recovered diethyl carbonate (300 g.) and phenylethylmalonic ester (166.6 g.)

boiling between 130 Cat 30 mm. and 142 c. at

4 mm. .Assuming the product to be pure phenylethylmalonic ester the yield based on ethyl phenylacetate was about 84% of the theoretical. The identity and purity of the product phenylethylmalonio ester was established by condensing a sample of it with urea. A high yield of phenobarbital, melting at 1'75--1'76 C., was obtained.

The yield and purity of the phenobarbital was as good as is usually obtained from pure diethyl phenylethylmalonate made by other methods.

Carrying out the above carbalkoxylation without the simultaneous removal, by distillation, of the alcohols produced in the reaction, is entirely feasible, but the yield is somewhat decreased.

EXAMPLE 2 Ethyl phenylacetate Sodium ethylate substantially free of alcohol was prepared as follows: Sodium (18 g.) was dissolved in anhydrous ethyl alcohol (350 ml.) in a 1 liter, three-necked flask; the flask was arranged for distillation and heated by an oil bath until no more alcohol distilled when the temperature of the bath was 165 C. After cooling, the sodium ethylate remained as a solid cake containing alcohol of crystallization. Diethyl carbonate (450 'ml.) and ethyl phenylacetate (123 g.) were added to the cooled sodium ethylate and the reaction mixture was stirred and warmed to about 60 C. for one hour during which the solid dissolved. The flask was connected to a fractionating column and alcohol was distilled at 150 mm. pressure. Alcohol was collected at 42-45 C. at 150 mm., and then the temperature at the head of the column rose rapidly to 74 C. at 150 mm.,

which corresponds approximately to the boiling point of diethyl carbonate. The formation of no more alcohol after arriving at this state showed that the carbalkoxylation reaction had been completed. The reaction mixture was cooled, acidified with acetic acid (4'7 m1,) and agitatedwith ice water. The water layer was separated and extracted with a little ether. The organic layers were combined, washed with water, dried over calcium chloride and distilled until all diethyl carbonate had been removed. The residue was distilled from. a Claisenflask at reduced pressure, yielding recovered ethyl phenylacetate (8 g.) and substantially pure diethyl phenylmalonate (134 g.), boiling point 129-130 C,, at 2 mm. The yield of diethyl phenylmalonate was 75% of the theoretical based on ethyl phenylacetate introduced into the reaction.

The foregoing and subsequent examples may be carried out, if desired, by placing the dialkyl carbonate and the ester in a flask under a reflux,

and then gradually dl'QiDltig in the metal alcoholate, which is preferably dissolved in alcohol. Simultaneously the alcohol is preferably taken off as a distillate at the head of the column.

If desired, the reactions described herein may be carried out at atmospheric pressure, rather than under reduced pressure. The selection of operating pressures is determined merely by manipulative convenience, in most instances.

EXAMPLE 3 Methyl phenylacetate Into a 500 ml. flask equipped with a stirrer were placed dimethyl carbonate (150 ml.). alcohol-free sodium methylate (19 g.), and methyl phenylacetate (50 g.). The mixture was stirred and warmed at 50 to 60 C. for two hours, and then the flask was attached to a distillation column and fractionated at 350 mm. pressure, until the boiling point of the product was 65 C., and a sample was insoluble in water. This showed that all the methyl alcohol formed by the reaction had been removed. Acetic acid (25 ml.) and ice water (150 ml.) were added, and the mass was agitated thoroughly. The organic layer was separated and distilled through a fractionating column, obtaining at first dimethyl carbonate, boiling at C. at atmospheric pressure, and recovered methyl phenylacetate (16 g.) boiling at 84 C. at 4 mm. and finally, dimethyl phenylmalonate (39 g.), which distilled at about 122 C. at 3 mm. pressure. The melting point of the dimethyl phenylmalonate produced was 47-to 48 C. The dimethyl phenylmalonate produced represented a yield of 84% of-the theoretical, based upon the amount of methyl phenylacetate not recovered.

EXAMPLE 4 Prom l phenylacetate Potassium metal (10 g.) was dissolved in anhydrous n-propyl alcohol ml.) and distilled until no more alcohol was removed when heated at 100 C. and 35 mm. pressure. After cooling, di-n-propyl carbonate (200 g.) and n-propyl phenylacetate (45 g.) were added. After stirring for about an hour, the flask was attached to a fractionating column and distilled under a pressure of 100 mm. until no more propyl alcohol, boiling at 53 C., was obtained as distillate, and the temperature rose quickly to 99 C., the boiling point of dipropyl carbonate at 100 mm. After cooling the reaction mixture, it was acidified with acetic acid (17 ml.) and agitated with ice water. The organic layer was-separated and fractionated at reduced pressure. At first dipropyl carbonate was obtained, then propyl phenylacetate (13 g.),distilling at 95 to C. at 5 mm. pressure, and finally. di-n-propyl phenylmalonate (38.2 g.) distilling at 146 to 148 C. at 4 mm. pressure. 'The yield of di-n-propyl phenylmalonate was 80%, based upon the acetate consumed.

lxmru: 5

Ethyl p-methylphenylacetate Sodium (5.6 g.) was added to anhydrous ethyl alcohol (150 ml.) in a 500 ml. three-necked flask attached to a fractionating column. When the reaction was complete the flask was heated by an oil bath until no more alcohol distilled when the temperature of the bath was C. and the pressure was 20 mm. After cooling, the sodium ethylate remained as a solid cake containing alcohol of crystallization. The cake was mechanically broken up and diethyl carbonate (250 ml.)

was added. The flask was arranged with a stirrer and the remaining alcohol was fractionated out at 150 mm. pressure and a bath temperature of 100 C.

The resulting alcohol-free suspension. of sodium ethylate in diethyl carbonate was cooled to 25 C. Ethyl p-methylphenylacetate (44 g.) was added over one-half hour. The mixture was heated to 90 C. and alcohol (45 ml.) was fractionated out over 2.5 hours at a pressure of 150 mm. The mixture was then cooled and decomposed with acetic acid and water. The organic layer was separated, washed free of acid, dried and then fractionated. A yield of 65% (43 g.) of diethyl p-methylphenylmaionate, boiling point 124-125" C. at 1-2 mm., and n 1.4930, was obtained. The ester was'identifled by converting it by alkaline hydrolysis to the known p-methylphenylmalonic acid, melting'at 142-143 0.

Exam? 6 Ethyl p-lodophenzllacetate A mixture of sodium ethylate /4 moi) and diethyl carbonate (250 ml.) was prepared as in Example 5. Then at 20 0., ethyl p-lodophenylacetate (72 g.) was added. .The mixture was heated to 90 C. at a pressure of 150 mm. and alcohol (30 ml.) was fractionated out at 35-40" C. over a period of one hour. After another 15 ml. of distillate was taken off the temperature of the distillate was 70 C. showing that all the alcohol formed had been removed. The mixture was worked up as in Example 5 and a yield of 61% (55 g.) of diethyl p-iodophenylmalonate was obtained boiling at 165 C. at 1.5 mm. and having an index of refraction of a 1.5432 to 1.5438. The saponiflcation equivalent of this material was found to be 181, which is the theoretical value for this ester. The compound was analyzed and found to contain 42.8% carbon and 4.1% hydrogen. Theory: Carbon 43.1%, hydrogen 4.1%.

ExAMrLa' 7 Ethyl homoveratrate A mixture of sodium ethylate (A mol) and diethyl carbonate (250 ml.) was prepared as in Example 5. Ethyl homoveratrate (56- g.) was then added to the mixture at room temperature and at atmospheric pressure during fifteen minutes. Most of the sodium ethylate went into solution and the latter become colored brown. The pressure was then reduced to 150 mm., the bath temperature was raised to 90-100 C., and 50 ml. of distillate was fractionated out at 30-50" C. within 1.5 hours. Then no more alcohol was formed and the distilling temperature rose to -70 C. The mixture was cooled with an ice water bath to around 20 C. and worked up as in Example 5. There was obtained at 68% (45 g.) yield of diethyl 3,4-dimethoxyphenylmalonate of boiling point 169170 C. at 1 mm. and index of refraction, n 1.5072-1.5080. The theoretical saponiflcation equivalent is 148 and that found was 149. The compound was analyzed and found to contain 60.9% carbon and 6.9% hydrogen. Theory: Carbon 60.8%, hydrogen 6.7%.

EXAMPLE 8 Ethyl a-naphthylacetate Sodium ethylate was prepared by dissolving sodium (1.4 g.) in anhydrous alcohol (50 ml.), and the solution was distilled to dryness and heated at 100 C. under 35 mm. pressure until no more alcohol could be removed. After cooling the residue, a solution of ethyl a-naphthylacetate (10 g.) in diethyl carbonate (150 ml.) was added. The reaction mixture was stirred and warmed until it refluxed under a packed column at 200 mm. pressure. Alcohol was removed as distillate from the head of the column, 15 ml. being obtained at 50 to 55 C. under 200 mm. pressure. The temperature then rose to 84 C. under 200 mm. pressure, which corresponds approximately to the boiling point of diethyl carbonate. The reaction mixture was cooled and poured onto ice andacetic acid (5 ml.), and the organic layer was separated and washed with water. After the solvent was distilled off until no more distillate was obtained at 35 mm. pressure and a bath temperature of 0., there remained 13 g. of an oil as residue. Addition of petroleum ether caused the residue to crystallize, and the solid was filtered and washed with petroleum ether. It was dissolved in a little anhydrous alcohol and crystallized by the addition of petroleum ether. The crystals obtained melted at 59 to 60 C. These were diethyl a.- naphthylmalonate. The yield was 67%.

EXAMPLE 9 Ethyl s-phenylpropz'onate Sodium ethylate substantially free of alcohol was prepared from 8 g. of sodium, as described in Example 2. Diethyl carbonate (250 ml.) and ethyl p-phenylpropionate (60 g.) were added to the cooled sodium ethylate. The flask was connected to a fractionating column and the reaction mixture was stirred and heated. Alcohol (70 mi.) boiling at 70-80" C. was obtained as distillate in five hours. After cooling the reaction mixture was acidified with acetic acid (25 ml.) and agitated with ice water. The organic layer was separated, washed with water, dried and distilled. After the diethyl carbonate had been removed, diethyl benzylmalonate (55.6 g.), boiling at about C. at 1 mm., was obtained. The index of refraction of the product was about 11, 1.484.

The identity of the product was proved by converting it to benzylmalondiamicle by shaking a portion of the distillate (2 ml.) with concentrated ammonia water (5 ml.) and keeping over night. On the following day the needles which had separated were filtered off, washed with ether and water and dried. The benzylmalondiamide melted at 229-230 0.

EXAMPLE 10 Ethyl acetate A mixture was made of sodium ethylate moi) and diethyl carbonate (250 ml.) as in Example 5. The flask containing the mixture was arranged with a stirrer and a reflux condenser. The mixture was stirred and heated at -125 C. and ethyl acetate (44 g.) was added during one hour. The mixture was then stirred and refluxed one hour at a bath temperature of -125 C. Then '55 ml. of distillate was fractionated out during 1.5 hours at 70-80 C. Then the distilling temperature rose rapidlyto 90 C. The mixture was cooled and worked up as in Example 5. There were obtained a 30% (26 g.) yield of diethyl malonate, boiling point 100-105 C. at 27 mm. and index of refraction n 1.4110-1.4113, and a 10% 10 g.) yield of tricarbethoxymethane, boiling point 123 C. at 6 mm. and index of refraction n 1.4227, and melting point 24-26 C. The diethyl malonate was identified by preparing from it malondiamide of melting point 172- 174 C.

ExAMPLs 11 Ethyl butyrate A mixture was made of sodium ethylate mol) and diethyl carbonate (250 ml.) as in Example 5. The mixture was heated to a bath temperature of 130 C. and stirred, and ethyl butyrate (58 g.) was added over a period of one hour. The bath temperature was then raised to 145-150 C, and during 4.5 hours 50 ml. of ethyl alcohol was fractionated out. The product was worked up as in Example 5. There was obtained a yield of 44% (41 g.) of diethyl ethylmalonate, boiling at 94-96 C. at 13 mm. pressure and having an index of refraction of n 1.4170.

There was also obtained a (9 g.) yield of diethyl diethylmalonate. The total product yield was about 55%. It will be noted that in this instance, as in several examples subsequently, diethyl carbonate apparently acts as an ethylating agent, as well as taking part in the carbalkoxylation.

The diethyl ethylmalonate was identified by hydrolyzi-ng it to give ethylmalonic acid, melting at Ill-113 C. The diethyl diethylmal-onate was identified by hydrolyzing it to give diethylmalonic acid, melting at 126-128 C.

EXAMPLE 12 Ethyl caproate A mixture was made of sodium ethylate /2 mol) and diethyl carbonate (400 ml.) as in Example 5. This mixture was stirred and heated to a bath temperature of 150155 C. and ethyl caproate (72 g.) was added during /2 hour. Then, during three hours, ethyl alcohol (55 ml.) was fractioned out at atmospheric pressure. The mixture was cooled and worked up as in Example 5. There were obtained a yield of 26% (2'7 g.) of diethyl butylmalonate, boiling at 136- 137 C. at 21 mm. and having an index of refraction, n 1.4250, and a yield of 34% (41 g.) of diethyl ethylbutylmalonate, boiling at 124 C. at 12 mm. and having an index of refraction of 11 1.4280. The esters were identified by hydrolysis to the corresponding malonic acids.

EXAMPLE 13 Ethyl stearate Sodium ethylate substantially free of alcohol was prepared from 2.4 g. of sodium, as described in Example 2. Diethyl carbonate (150 ml.) and ethyl stearate (31 g.) were added to the cooled sodium ethylate and the reaction mixture was stirred and refluxed under a column at 250 mm. pressure for hour. Then the reaction mixture was refluxed at atmospheric pressure and alcohol (9.1 g.) was obtained as distillate during three hours. The temperature at the head of the column rose to 125 C., the boiling point of diethyl carbonate, and no more alcohol could be obtained. The excess diethyl carbonate was distilled off as completely as possible at reduced pressure leavinga waxy solid. The residue was agitated with ether, acetic acid (10 ml.) .and

water, and the organic layer was separated,.

washed and dried. Evaporation of the ether gave 40 g. of an oil which solidified at about 10 C. This was distilled yielding diethyl cetylmalonate (27.8 g.), boiling at 185-190 C. at 1 mm. The identity of the product was proved by hydrolyzing it to cetylm'alonic acid. A portion of the distillate (11 g.) was refluxed for three hours with potassium hydroxide (8 g.) in alcohol ml). The alcohol was evaporated and the residue was dissolved in water and acidified with hydrochloric acid. The oil was extracted with ether and the extract was evaporated to dryness. The residue was recrystallized from acetic acid and washed with petroleum ether. The cetylmalonic acid melted at 117-120 C.

EXAMPLE 14 Butyl stearate Potassium metal (20 g.) was dissolved in n-butyl alcohol (200 cc.) in a 1 liter, threenecked flask. The flask was arranged for distillation at reduced pressure and heated by an oil bath until no more distillate was obtained when the temperature of the bath was about C., and the pressure was about 30 mm. After cooling, the potassium butylate remained as a solid cake containing some butyl alcohol of crystallization. Di-n-butyl carbonate (435 g.) and butyl stearate (170 g.) were added. The flask was fitted with a mechanical stirrer and attached to a fractionating column. Butyl alcohol was fractionated out of the reaction mixture at 54-60 C.

at 50 mm. pressure. When no more butyl alcohol Was obtainable as distillate the reaction mixture was cooled and poured onto ice and acetic acid (35 00.). The organic layer was separated and distilled through a column at reduced pressure until all dibutylcarbonate had been removed. The residue was distilled from a Claisen flask at reduced pressure. Dibutyl cetylmalonate (123 g.) was obtained, boiling at about 206-215 C. at 2 mm.,n 14432-14441.

EXAMPLE 15 Ethyl iso-valerate A mixture of sodium ethylate (0.4 mol) and diethyl carbonate (300 ml.) was made up as in Example 5. The mixture was stirred and ethyl iso-valerate (52 g.) was added. Then, during twelve hours, 25' ml. of distillate, mostly ethyl alcohol, was fractionated out at atmospheric pressure and a bath temperature of 1'70-175 C. The mixture was cooled and worked up, as described in Example 5. There were obtained yields of 30% (26 g.) of diethyl iso-propylmalonate, boiling at 106-109 C. at 18 mm.'and having an index of refraction of n 1.4186- 1.4190, and 10% (7 g.) of diethyl ethyl-iso-propyl-malonate of boiling point 114 C. at 18 mm. and having an index of refraction of n 14282-14300. The diethyl iso-propylmalonate was identified by hydrolyzing it to iso-propylmalonic acid, melting at 88-90 C. The diethyl ethyl-iso-propylmalonate was identified by hydrolyzing it to ethyl-iso-propylmalonic acid, melting at 132134 C.

EXAMPLE 16 Ethyl iso-amylacetate A mixture of sodium ethylate (0.28 mol) and diethyl carbonate (250 ml.) was prepared as in Example 5, andethyl iso-amylacetate (45 g.) was added. The mixture was stirred at a bath temperature of -160 C. During three hours, 33 m1. of ethyl alcohol was fractionated out, and the mixture was then refluxed for three hours longer. It was worked up in the manner described in Example 5. Yields of 25% (15 g.) of diethyl iso-amylmalonate, of boiling point 130 C. at 16 and of 45% (30 g.) of diethyl isoamylethylmalonate, boiling point 135 C, at 16 mm., were obtained. The diethyl iso-amylmalonate was identified by hydrolyzing it to iso-amyimalonic acid, which melted at 100-102" C. The diethyl iso-amylethylmalonate was identified by hydrolyzing it to ethyl-ismamylmalonic acid, which melted at 120-121 C.

EXAMPLE 17 Butyl laurate Potassium metal g.) was dissolved in n-butyl alcohol (100 ml.) and the solution was distilled to drynessat reduced pressure. Dibutyl carbonate (350 ml.) and butyl laurate (77 g.) were added to the cooled residue. Butyl alcohol was fractionated out of the reaction mixture according to the procedure described in Example 14, a total of 88 g. of distillate being obtained in' three hours, boiling at 47-404 C. at 25 mm. The reaction mixture was cooled and poured onto ice and acetic acid (25 ml.) and the organic layer was separated, washed and dried. After distilling off the excess dibutyl carbonate there was obtained di-n-butyl decylmalonate (65.4 g.) boiling chiefly at 159160 C. at 1.5 mm. The index of refraction of the product was ri 1.4390. Its identity was proved by determination of the saponification equivalent: Found 179.3 and 180.9; calculated for C21H40O4, 178.1.

EXAMPLE 18 Ethyl laur te Sodium ethylate was made by dissolving sodium metal (7.5 g.) in anhydrous alcohol (150 ml.) and distilling themixture to dryness. After cooling, dry diethyl carbonate (300 ml.) and ethyl laurate (68 g.) were added. The reactants were stirred and refluxed under a packed column at 200 mm. pressure, and alcohol was removed as distillate. After two hours, very little more alcohol was obtained, and the mixture was refluxed at atmospheric ressure for two hours more. After cooling the mixture was acidified with acetic acid (20 ml.), and shaken with water. The organic-layer was washed, dried and distilled. After removing the diethyl carbonate, diethyl decylmalonate (45 g.) was obtained. v

The product distilled at about '130-132 C. at 1.5 mm., and its index of refraction was 11. 5, 1.4341. Its identity was further established by converting it to the free acid. The product was hydrolyzed by refluxing for three hours with p0- tassium hydroxide g.) dissolved in alcohol (200 ml.). The alcohol was evaporated, the residue was dissolved in water and decylmalonic acid was precipitated by adding excess hydrochloric acid. After recrystallizing from a mixture of chloroform and petroleum ether it melted at 118-1195 0..

The neutral equivalent found was 122.2 and calculated for Cl3H2404 is 122.1.

EXAMPLE 19 Ethyl oleate Sodium ethylate substantially free of alcohol was prepared from 8.5 g. of sodium, as described in Example 2. Diethyl carbonate (450 ml.) and ethyl oleate (83 g.) were added to the cooled sodium ethylate. The ethyl oleate was prepared by esterification of oleic acid U. S. P. and was not quite pure, as shown by its saponification equivalent being 327, compared to the theoretical of 310. The reactants were stirred and refluxed under a pressure of 200 mm. for two hours and then distilled through a column at atmospheric pressure until no more alcohol could be obtained.

The reaction mixture was cooled and agitated with excess acetic acid and ice water and the organic layer was separated, washed with water and dried. After removing the diethyl carbonate by distillation diethyl hexadecenylmalonate was.

EXAMPLE 20 Ethyl sebacate Sodium (9.6 g.) was dissolved in ethyl alcohol (200 ml.). and the mixture distilled to dryness. The sodium ethylate remaining as residue was 44.2 g. After cooling, diethyl carbonate (200 ml.) and ethyl sebacate (50 g.) were added, and the mixture was stirred and heated under a packed column at 150 mm. pressure. Alcohol (21 g.), boiling at 42 to 44 C. at 150 mm. pressure was removed as distillate during two hours, and then the reaction mixture was heated at atmospheric pressure, and 23 g. more distillate were obtained in the following two hours. After cooling, the reaction mixture was acidified with acetic acid (25 ml.), and poured onto ice. The organic layer was separated, washed and distilled. After all the solvent had been removed, the residue weighed 67 g. The oil was distilled from a- Claisen flask and 1,1,8-tricarbethoxyoctane, boiling at 185 C.

under 1.5 mm. pressure, with some decomposition,

l was obtained. The composition of the product was established by determining its saponification equivalent; found 111.4; calculated for Ci'zHaoOc, 110.

Carrying out the above carbalkoxylation reactions without the simultaneous removal by distillation of the alcohol produced in the reaction. is entirely feasible, but the yield is somewhat decreased. a

It will be noted that several different procedures are utilized in carrying out the foregoing examples. Any of the procedures employed may be utilized in carrying out any particular reaction, for example, the dialkyl carbonate and the ester to be carbalkoxylated may be placed in a flask under a reflux, and the metal alcohol-ate gradually. dropped in, or the dialkyl carbonate and the alcoholate may be placed in a flask and the ester to be carbalkoxylated dropped in. In either instance, the alcohol is preferabiy taken off as a distill-ate at the head of the column.

The alkali metals themselves are unsuitable substitutes for the metal alcoholates employed in carrying out the present invention. These alkali metals react with and decompose the dialkyl carbonate.

The foregoing reactions may be carried out at atmospheric, or under reduced pressure. The

selection of operating pressures is in most inseveral objects of the invention are achieved and other advantageous results attained,

As many changes could be made in the above processes without departing from the scope of the invention, it is intended that all matter contained in the above description shall be interpreted as illustrative and not in a limiting sense.

We claim:

1. A process for simultaneously carbalkoxylating and metallating an ester of the type:

' where R is an aryl radical and R' is a hydrocarbon radical, which comprises mixing said ester with an anhydrous alkali metal alcoholate and a large excess of a dialkyl carbonate over that required as a reactant, whereby one of the hydrogens of the CH2 group is replaced by a carbalkoxyl group and the other hydrogen is replaced by an alkali metal.

2. A process for simultaneously carbalkoxylating and metallating an ester of the type:

where R is an aryl radical and R is a hydrocarbon radical, which comprises mixing said ester with an anhydrous alkali metal alcoholate and a large excess of a dialkyl carbonate over that required as a reactant, and continuously subjecting the mixture to distillation for removing alcohol from the reaction mixture, whereby one of the hydrogens of the CH2 group is replaced by a earbalkorwl group and the other hydrogen is replaced by an alkali metal.

III

4. A process for simultaneously carbalkoxylating and metallating ethyl homoveratrate which comprises mixing and heating said compound with anhydrous sodium ethylateand a large excess of diethyl carbonate, the quantity thereof being sufflcient to function as reagent and as reaction medium.

5. A process for simultaneously carbalkoxylating and metallating ethyl a-naphthylacetate which comprises mixing and heating said compound with anhydrous sodium ethylate and a large excess of diethyl carbonate, the quantity thereof being sufficient to function as reagent and as reaction medium.

6, A process for simultaneously carbalkoxylating and metallating ethyl homoveratrate which comprises mixing and heating said compound with anhydrous alcohol-free sodium ethylate and a large excess of diethyl carbonate, the quantity thereof being sufllcient to function as reagent and as reaction medium, and continuously subjecting the mixture to distillation for removing alcohol formed by the reaction.

7. A process for simultaneously carbalkoxylating and metallating ethyl a-naphthylacetate which comprises mixing and heating said compound with anhydrous alcohol-free sodium ethylate and a large excess of diethyl carbonate, the quantity thereof being sufficient to function as reagent and as reaction medium, and continuously subjecting the mixture to distillation for removing alcohol formed by the reaction.

VERNON H. WALLINGFORD. AUGUST H. HOMEYER.

REFERENCES CITED The following references are of record in the file-of this patent:

UNITED STATES PATENTS Number Name Date 2,346,059 Wallingford et al. Apr. 4, 1944 2,367,632 Wallingford Jan. 16, 1945 OTHER REFERENCES Nelson et al., Journal American Chemical Society, vol. 50, pages 2758 to 2762 (1928).

Lux, Berichte, vol. 62, pages 1824 to 1827 (1929). 

